This study was designed to assess the influence of efflux pump activity on the biofilm formation in Salmonella Typhimurium. Salmonella enterica subsp. enterica serovar Typhimurium ATCC 19585 (ST^WT) and clinically isolated S. Typhimurium CCARM 8009 (ST^CI) were treated with ceftriaxone (CEF), chloramphenicol (CHL), ciprofloxacin (CIP), erythromycin (ERY), norfloxacin (NOR), and tetracycline (TET) in autoinducer-containing media in the absence and presence of phenylalanine-arginine β-naphthylamide (PAβN) to compare efflux pump activity with biofilm-forming ability. The susceptibilities of ST^WT and ST^CI were increased in the presence of PAβN. ERY+PAβN showed the highest decrease in the minimum inhibitory concentration (MIC) of ERY from 256 to 2 μg/mL against ST^WT and ST^CI. The antimicrobial activity of NOR against planktonic cells was significantly increased in the presence of PAβN, showing the lowest numbers of ST^WT (3.2 log CFU/cm²), and the TET+PAβN effectively inhibited the growth of ST^CI (5.2 log CFU/cm²). The lowest biofilm-forming abilities were observed at NOR+PAβN against ST^WT (biofilm-forming index, BFI < 0.41) and CEF+PAβN against ST^CI (BFI = 0.32). The bacteria swimming motility and relative fitness varied depending on the antibiotic and PAβN treatments. The motility diameters of ST^WT were significantly decreased by NOR+PAβN (6 mm) and TET+PAβN (15 mm), while the lowest motility of ST^CI was observed at CIP+PAβN (8 mm). The significant decrease in the relative fitness levels of ST^WT and ST^CI was observed at CIP+PAβN and NOR+PAβN. The PAβN as an efflux pump inhibitor (EPI) can improve the antimicrobial and anti-biofilm efficacy of antibiotics against S. Typhimurium. This study provides useful information for understanding the role of efflux pump activity in quorum sensing-regulated biofilm formation and also emphasizes the necessity of the discovery of novel EPIs for controlling biofilm formation by antibiotic-resistant pathogens.

In this study, the synergistic antibacterial and antibiofilm effects of the traditional herb C. ambrosioides L. and the classic antibiotic penicillin G on MRSA provide a potential strategy to deal with the rapid development of MRSA antibiotic resistance. This study also provides a theoretical basis for further optimizing the combined effect of kaempferol rhamnosides, quercetin, and penicillin G and exploring anti-MRSA biofilm infection research with SarA and σB as drug targets.

As many countries implement different programs aimed at eliminating malaria, attention should be given to asymptomatic carriers that may interrupt the progress. This was a community-based cross-sectional study conducted in Tanzania from December 2022 to July 2023 within 4 villages from each of the 3 regions, Geita and Kigoma, which are high malaria transmission, and Arusha, which is low transmission. Malaria was diagnosed in asymptomatic individuals aged 1 year and older using the malaria rapid diagnostic test and light microscope. A total of 2,365 of 3,489 (67.9%) participants were enrolled from high-transmission villages. The overall prevalence was 25.5% and 15.8% by malaria rapid diagnostic test and light microscope, respectively. Using the respective tools, the prevalence was significantly higher at 35.6% (confidence interval (CI)=23.6–49.9) and 23.1% (CI=16.2–35.1) in the high-transmission regions (Geita and Kigoma) compared with 2.9% (CI=1.1–3.5) and 1.1% (CI=0.7–1.8) in the low-transmission region (Arusha). Children younger than 15 years and males accounted for the greatest proportion of infections. In the study area, the prevalence of asymptomatic cases was higher than that of reported symptomatic cases in health facilities. We hypothesize that these parasite reservoirs may contribute to the persistence of malaria in the country. Therefore, to achieve comprehensive malaria control in the country, the surveillance and screening of asymptomatic malaria cases are vital.

Plasmodium vivax serological exposure markers (SEMs) have emerged as promising tools for the actionable surveillance and implementation of targeted interventions to accelerate malaria elimination. To determine the dynamic profiles of SEMs in current and past P. vivax infections, we screened and selected 11 P. vivax proteins from 210 putative proteins using protein arrays, with a set of serum samples obtained from patients with acute P. vivax and documented past P. vivax infections. Then we used a murine protein immune model to initially investigate the humoral and memory B cell response involved in the generation of long-lived antibodies. We show that of the 11 proteins, especially C-terminal 42-kDa region of P. vivax merozoite surface protein 1 (PvMSP1-42) induced longer-lasting long-lived antibodies, as these antibodies were detected in individuals infected with P. vivax in the 1960-1970s who were not re-infected until 2012. In addition, we provide a potential mechanism for the maintenance of long-lived antibodies after the induction of PvMSP1-42. The results indicate that PvMSP1-42 induces more CD73⁺CD80⁺ memory B cells (MBCs) compared to P. vivax GPI-anchored micronemal antigen (PvGAMA), allowing IgG anti-PvMSP1-42 antibodies to be maintained for a long time.

Objective: To compare the predictive performance of the novel Cholesterol, High-Density Lipoprotein, and Glucose (CHG) index for the incident type 2 diabetes mellitus (T2DM) versus the established indices—triglyceride-glucose (TyG), atherogenic index of plasma (AIP), and metabolic score for insulin resistance (METS-IR). Methods: A longitudinal cohort study was performed on 15, 453 participants from the NAGALA cohort (2004–2015) without baseline T2DM. The CHG index was calculated from total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and fasting blood glucose (FBG). Several additional indices were established, including the TyG, AIP, and METS-IR. Cox regression, Kaplan-Meier analysis, restricted cubic spline (RCS) analysis, and time-dependent receiver operating characteristic (ROC) curves were performed to determine the predictive performance, after adjusting for various confounders (e.g., obesity, liver function). Robustness was assessed through sensitivity analyses. Results: During a 6.13-year follow-up, 373 T2DM cases were recorded. In the fully adjusted models, we found that the CHG index had the highest hazard ratio (HR): 6.18 per unit (95% CI: 3.38–11.27), outperforming the TyG index (HR: 1.39), AIP (HR: 1.80), and METS-IR (HR: 1.07). Quartile analysis revealed a dose-response relationship for CHG (Q4 HR: 4.36 vs. Q1, P < 0.001). Further, the RCS analysis revealed a linear association between CHG and T2DM risk ( P for overall trend < 0.001; P for nonlinearity = 0.712). Moreover, the CHG index achieved a satisfactory discriminative accuracy (based on the area under the curve [AUC]: 0.783 vs. TyG: 0.751, AIP: 0.745, METS-IR: 0.780) and its predictive power was consisted over the 12 years (peak AUC: 0.798 at 7 years). Sensitivity analyses for various subgroups (e.g., non-obese, non-fatty liver) confirmed that the obtained results were robust. Conclusions: The CHG index that integrates cholesterol, HDL-C, and glucose metabolism, showed superior predictive performance for the incidence of T2DM. Suggesting that it effectively captures the multifactorial pathophysiology of the disease. It is based on routine biomarkers making it easily applicable in risk stratification, offering a cost-effective tool for early intervention and precise prevention in clinical and public health settings.

To verify the size and emergence time of new permeability pathways (NPPs) in malaria parasites, the permeability of the Plasmodium falciparum-infected erythrocytes was tested with different particle sizes of nanomaterials by flow cytometry assay. The results confirmed the permeability of the host cell membrane increases with parasite maturation for the stage-development evolution of NPPs, and especially found that a particle size of about 50 nm had higher efficiency. As a kind of the novel nanomaterials, nitrogen-doped carbon dots (NCDs) showed no toxicity, specificity binding ability to the malaria parasites, and could label live elder blood-stage P. falciparum through NPPs, indicating the potential application in cell imaging. NPPs and some nanomaterials such as NCDs deserve more attention and exploration for the elimination and prevention of malaria.